Post-traumatic stress disorder (PTSD) is a major public health problem and is often intractable to available treatments. The broad, long-range objective of this proposal is to identify abnormalities of rapid eye movement sleep (REMS) and startle behavior that reflect the essential pathophysiology of PTSD, i.e., abnormalities that are consequences of exposure to a traumatic environmental stressor. Such abnormalities will be distinguished from physiological findings that are determined genetically, and by early-life environmental influences. A history of alcohol abuse, which possibly influenced earlier physiological studies of PTSD, will be minimized as a confounding variable. The broad aim of the proposal will be addressed using a co-twin control design, by studying the sleep and startle behavior of a sample of monozygotic (MZ) twins drawn from the over 2,000 MZ twin-pairs of the Vietnam Era Twin (VET) Registry. The first specific aim is to compare the sleep and sleep mentation of 30 MZ twin-pairs discordant for the PTSD phenotype. It is hypothesized that measures of REMS phasic activity will be evaluated in the PTSD subjects, as will measures of dream recall. The second specific aim is to compare the startle behavior of members of MZ twin-pairs discordant for service in Southeast Asia and for the PTSD phenotype. It is hypothesized that acoustic startle amplitude will be larger in the PTSD subjects, that pre-pulse inhibition of acoustic startle will be decreased, and that the cognitive factor, expectation of stimulus occurrence, will be less effective in inhibiting startle in the PTSD subjects. In order that subjects not cross time zones in traveling to the test site and thereby experience jet lag, sleep laboratories in the Eastern, Central, and Pacific time zones will be used. Standard polysomnographic techniques will be used to study the subjects' sleep over three consecutive nights; the first night will be adaptational, the second night will yield standard sleep measures, and the third night will provide dream recall data. The baseline amplitude of acoustic startle, the pre-pulse inhibition of startle, and the modulation of startle by the cognitive, expectancy factor will be assessed on intervening days by recording the eyeblink response electromyographically.